Congenital Rubella Surveillance

Pat Tookey

National Congenital Rubella Surveillance Programme

UCL Institute of Child Health, London, UK

NCRSP / ICH / 2012

Rubella and CR surveillance in the UK

• Health Protection Agency and Health Protection Scotland – Acquired infection, notifications and laboratory confirmed cases,

including rubella in pregnant women, (male/female ratio)

– Serosurveys (eg based on antenatal screening samples)

– Immunisation uptake data (COVER / measles)

• Infectious Diseases in Pregnancy Screening Programme – National and regional data on uptake and outcome of infection

screening, including rubella susceptibility

• Office for National Statistics / NHS Information Centre – Terminations for rubella contact, disease, vaccination in pregnancy

• National Congenital Rubella Surveillance Programme

COVER data (HPA & HPS) MMR1 reported uptake by 24 months, 1996-2011

70

75

80

85

90

95

100

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

England Wales Scotland

NCRSP / ICH / 2012

In England,

85% had MMR2

by age 5 in 2011

Antenatal screening

• Routine offer of rubella susceptibility screening in place for 40 years

• Antenatal screening standards updated 2011

• Rubella susceptibility uptake >95%

• Approximately 4% screen susceptible

• MMR should be given after delivery, before discharge, with second dose by GP

• But delivery of post-partum MMR variable

• Policy currently under review

• Alternatives?

http://infectiousdiseases.screening.nhs.uk/standards

Rubella seroprevalence in ethnically diverse population of pregnant women in London, 2004 • 18,882 newborn screening blood spot samples

• Maternal rubella IgG antibody levels measured

• Latent class regression finite mixture models used to classify samples as seronegative to rubella

• Estimated 2.7% (95% CI 2.4%–3.0%) seronegative

• Women born in Sub-Saharan Africa 4.2 (95% CI 3.1-5.6) times more likely to be seronegative than UK-born; those born in South Asia 5.0 (3.8–6.5) times more likely (aORs)

• Women under 25, and particularly under 20, significantly more likely to be seronegative than women in their early thirties

Hardelid et al, J Med Screen 2009;16:1–6

Audit of rubella IgG antibody status in antenatal women in a Welsh NHS Trust 2005–09 (12,000 pregnancies): susceptibility cut-off at <4 IU/ml and <10 IU/ml

0%

5%

10%

15%

20%

25%

all pregnancies first pregnancies

only

subsequent

pregnancies

first pregnancies

in women born

1987-92

<4 IU/ml <10 IU/ml

NCRSP / ICH / 2012

Matthews et al. Epidemiol and Infect 2010

Serprevalence of low rubella IgG antibody levels among antenatal women in England, 2004-2009

• 440,000 antenatal samples from ethnically mixed population, 25% black or minority ethnic group

• BME women twice as likely to be susceptible

• Among BME women with <10 IU/ml, 70% were <4

• Women born 1986-90 6 times more likely, born after 1990 30 times more likely, to be <10, than those born 1976-80

• Could not distinguish between UK and non-UK born, or assess by parity

Byrne et al, Vaccine 2012; 30: 161-167

NCRSP / ICH / 2012

NCRSP

1971-1989 Passive reporting by audiologists, GPs, other health professionals, originally to two registries (Leeds and London), and from 1985 to combined registry at Institute of Child Health, London

1990-date Active surveillance of Congenital Rubella through the British Paediatric Surveillance Unit mechanisms

Funding history • Originally funded by the Medical Research Council,

subsequently supported by PHLS/HPA and ICH, additional occasional support from Sense (charitable).

• Currently no funding – future uncertain

Monitoring effect of rubella

vaccination policy since 1971

NCRSP / ICH / 2012

BPSU active reporting scheme

• Established 1986

• Currently >3000 respondents: mainly consultant paediatrician members of the Royal College of Paediatrics and Child Health

• Response rate >94%

• Monthly report card sent to all respondents

• Respondents tick any reportable condition seen in the preceding month, or ‘nil return’ box, and return card to BPSU

• BPSU notifies ‘Positive’ returns to appropriate investigator, who contacts reporting clinician for further details

NCRSP / ICH / 2012

BPSU active reporting scheme • Case definition: Any infant (live or

still born) or child up to 16 years of age who, in the opinion of the notifying paediatrician, has suspected or confirmed congenital rubella with or without defects, based on history, clinical and/or laboratory findings.

• Please include “imported cases”, including children born in the British Isles where the maternal infection occurred abroad, AND children who were born abroad.

• Reporting instructions: Please report any infant (live or still born) or child seen by you for the first time in the last month who meets the case definition, REGARDLESS OF COUNTRY OF BIRTH.

• Germany

• Greece and Cyprus

• Ireland

• Latvia

• Netherlands ^

• Portugal

• Switzerland *

• Wales

• Australia *

• Canada

• Malaysia

• New Zealand *

• Papua New Guinea

http://www.inopsu.com

NCRSP / ICH / 2012

NCRSP information • Maternal details

– demographic information (age, ethnic group, parity)

– immunisation history and laboratory details

– time, type, symptoms of maternal infection

– ? imported infection (country of birth, date arrived)

• Infant details – demographics, clinical signs and symptoms at birth

– laboratory details

• Previously provided basis for longer term follow up of reported children and data on late sequelae

• Older cases ‘flagged’ for cancer & death registration

NCRSP / ICH / 2012

Control and decline of Rubella

• Selective rubella vaccination policy from 1970

– 1971 – 1975 average 50 CR births, 750 rubella associated terminations reported each year

– 1981 – 1985 40 births,150 terminations per year

– 1986 – 1988 30 births, 75 terminations per year

• MMR introduced 1988

– Immediate reduction in reported births and terminations

– 1990s – average 4 CR births, 8 terminations reported each year

– 2000s – average 1 or 2 CR births reported each year

NCRSP / ICH / 2012

Congenital rubella births (NCRSP) 1971-2011 and rubella associated terminations* (ONS) 1971-2000

0

10

20

30

40

50

60

70

80

71 73 75 77 79 81 83 85 87 89 91 93 95 97 99 '01 '03 '05 '07 '09 11

0

200

400

600

800

1000CR births (England,

Scotland, Wales)

Rubella-associated

terminations (England &

Wales)

MMR

*Terminations data not published since 2000 because of very low numbers

CR births (n) Terminations (n)

Maternal place of birth and infection CR infants born in England, Scotland, Wales, 1990-2010

0

2

4

6

8

10

12

14

90 92 94 96 98 '00 '02 '04 '06 '08 '10

Importedinfection

Born abroad,acquired ESW

Born ESW,acquired ESW

number of births

*1 British born woman, 1 born abroad but resident in UK many years

# Associated with outbreak in Greece, but maternal reinfection acquired in UK

Over 60 rubella-associated terminations reported in the same period

*

#

NCRSP / ICH / 2012

Key points

• Most recognised rubella infections in early pregnancy end in termination

• Most congenital rubella births are unexpected

• Most diagnosed reported CR infants have typical severe signs

• CRI or non-specific signs (including isolated hearing loss) now unlikely to be diagnosed and reported (few in recent years)

• BPSU active surveillance

– comprehensive national coverage

– highly sensitive to changes in birth prevalence of congenital rubella

NCRSP / ICH / 2012

Summary of UK position

• Few reported cases of rubella infection in pregnancy, rubella TOPs or congenital rubella (<1 in 100,000 live births since 1996) in recent years

• Fifteen years of inadequate MMR uptake

– mumps/measles outbreaks, rubella sporadic so far

• High rubella susceptibility in 1st generation immigrants

• Low vaccine uptake, ethnically mixed areas coincide

• Potential for importing infection

– frequency of travel between UK and countries of origin

NCRSP / ICH / 2012

CR(S) surveillance challenges

• Maintaining high quality active surveillance when cases rare (NB – feature of mass immunisation strategy is lengthening of epidemic cycle)

• Maintaining awareness of rubella, CR, importation of infection, among health care staff

• Sentinel surveillance – two major typical defects? Cataracts?

– But prevalence of specific defects depends on local circumstances/epidemiology, eg recognition of infection in pregnancy, availability of TOP for diagnosed pregnancies

NCRSP / ICH / 2012

CR(S) surveillance challenges

• Overall largest burden is hearing loss – how to identify? Especially if MMR for infants

• Role of (neonatal) hearing screening? Consider rubella?

• In some countries / situations most severely affected may not survive infancy

• Impact of miscarriage, intrauterine death, survival of pre-term or low birthweight infants, termination of pregnancy….

Acknowledgments

• RCPCH and British Paediatric Surveillance Unit

• All reporters to NCRSP over many years

• HPA, Sense and other funders and supporters

• Catherine Peckham

• London Research Ethics Committee

• National Information Governance Board

Ethics